短期間の炎症曝露がNLRP3インフラマソーム発現の調節を介して臍帯由来間葉系幹細胞の遊走と分化に及ぼす影響
Helsy Junaidi1,2, Dewi Sukmawati1,3, Anoop Narayanan V4
1Doctoral Program in Biomedical Science, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
Background:
An innovative approach for tissue restoration using Umbilical Cord-derived Mesenchymal Stem Cells (UC-MSCs) is hindered by their poor survival rate due to the detrimental effects of the injured tissue microenvironment. Activation of NLRP3 inflammasome in an inflammatory environment which is followed by cellular impairment, has been reported. However, the expression of NLRP3 inflammasome in UC-MSCs in response to the inflammatory environment is not well understood. This study aims to investigate the impact of short-term exposure to an inflammatory environment induced by Lipopolysaccharide (LPS) on hUC-MSCs, focusing on cell viability, migration, differentiation, and the expression of NLRP3 inflammasome-related genes.
Methods:
hUC-MSC were exposed to LPS at concentration of 10 and 50 μg/ml for 3 and 6 hr. Cell viability was assessed using CCK-8 assay, migration capacity was evaluated using a scratch test, and differentiation capacity and the expression of NLRP3 inflammasome-related genes were measured using qRT-PCR.
Results:
Short-term LPS induction did not affect the viability of hUC-MSCs but reduced their migration and differentiation capacity, particularly at 50 μg/ml for both time points (p<0.05). The induction caused an increase in the mRNA levels of NLRP3, TLR-4, and RelA/p65, which correlated with elevated expression of caspase-1 and IL-1β.
Conclusion:
Short-term exposure to LPS influences hUC-MSCs by upregulating NLRP3, TLR4/ReIA (p65), IL-1β, and caspase-1 mRNA levels, leading to impaired migration and differentiation ability. This study underscores the significant impact of short-term exposure to an inflammatory microenvironment on hUC-MSC, potentially compromising their migration and differentiation capacity through the NLRP3 pathway.
